Manage wisely: poly (ADP-ribose) polymerase inhibitor (PARPi) treatment and adverse events

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have transformed the treatment landscape in front-line and recurrent high-grade serous ovarian cancer. Maintenance strategies with PARPi have been assessed in randomized phase III trials in ovarian cancer; switch maintenance in the case of olaparib, niraparib, and rucaparib; and concurrent followed by continuation maintenance with veliparib. These studies have shown progression-free survival advantage with PARPi maintenance, with no major adverse changes in the quality of life; however, overall survival data remain immature to date. PARPi have also been incorporated in clinical practice as a single-agent treatment strategy in high-grade serous ovarian cancer, mainly in women who harbor alterations in the BRCA1/2 genes or have alterations in the homologous recombination deficiency (HRD) pathway. Contemporary studies are looking into potentially synergistic combination strategies with anti-angiogenics and immune checkpoint inhibitors, among others. The expansion of PARPi treatment has not been limited to ovarian cancer; talazoparib is licensed in patients with HER2-negative breast cancer with germline BRCA mutations (BRCAm), and front-line olaparib maintenance in patients with pancreatic cancer with germline BRCAm. Numerous studies assessing PARPi either in monotherapy or in combination with other agents are ongoing in multiple tumors, including prostate, endometrial, brain, and gastric cancers. Many patients are being treated with PARPi, some for prolonged periods of time. As a result, a thorough knowledge of the potential short- and long-term adverse events and their management is warranted to improve patient safety, treatment efficacy, and towards maintaining an appropriate dose intensity.

Keywords: ovarian cancer.

Figure 1

Maintenance strategies in phase III clinical trials assessing poly (ADP-ribose) polymerase inhibitor (PARPi) treatment in ovarian cancer.

Figure 2

Criteria that may help clinicians in poly (ADP-ribose) inhibitor (PARPi) treatment selection for ovarian cancer. EORTC, European Organization for Research and Treatment of Cancer; FACIT, Functional Assessment of Chronic Illness Therapy; HR Qol, health-related quality of life; ICER, incremental cost-effectiveness ratio; Pfs2, progression after the next line of therapy; PRO: patient-reported outcomes; QALY, quality-adjusted life-year; TFST, time to first subsequent therapy; TSST, time to second subsequent therapy; WTP, willingness to pay.